Hyperkinesia refers to an increase in muscular activity that can result in excessive abnormal movements, excessive normal movements or a combination of both. It is the opposite of hypokinesia , which refers to decreased bodily movement, as commonly manifested in Parkinson's disease. Many hyperkinetic movements are the result of improper regulation of the basal ganglia — thalamocortical circuitry. Overactivity of a direct pathway combined with decreased activity of an indirect pathway results in activation of thalamic neurons and excitation of cortical neurons, resulting in increased motor output. The word hyperkinesis comes from the Greek hyper , meaning "increased," and kinein , meaning "to move.

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Alternative titles; symbols. Infantile parkinsonism-dystonia, also known as dopamine transporter deficiency syndrome DTDS , is an autosomal recessive complex motor neurologic disorder with onset in infancy. Affected individuals show hyperkinesia with orolingual and limb dyskinesia, dystonia, and chorea, or hypokinesia with parkinsonian features, such as bradykinesia, rigidity, and tremor. Other features may include axial hypotonia, pyramidal tract signs, and eye movement abnormalities.

Many patients are misdiagnosed as having cerebral palsy. Cognitive function appears to be less severely affected, but most patients die in the teenage years. There is no effective treatment. Laboratory studies show an increased ratio of homovanillic acid HVA to 5-hydroxyindoleacetic acid 5-HIAA in cerebrospinal fluid CSF , which represents an increased ratio of dopamine to serotonin metabolites review by Kurian et al.

For an overlapping phenotype, see tyrosine hydroxylase deficiency , also known as autosomal recessive Segawa syndrome. Kurian et al. One family was of Pakistani origin and the other of European descent. Two patients were initially misdiagnosed with cerebral palsy. All had features of progressive parkinsonism, dystonia, pyramidal tract signs, and hypertonicity at examination between 6 and 12 months of age. There was evidence of global developmental delay, but later studies showed no psychiatric or behavioral abnormalities.

All patients showed a poor clinical response to multiple therapeutic agents. All parents were unaffected. The patients were ascertained from 7 pediatric neurology centers. All children presented with a movement disorder with onset in early infancy range 0. Before diagnosis, 7 children had been misdiagnosed with cerebral palsy. Symptoms were somewhat variable, but included neonatal irritability and early feeding difficulties, a hyperkinetic syndrome with dystonia and chorea, a predominantly hypokinetic syndrome with parkinsonism, or a mixed hyperkinetic and hypokinetic movement disorder.

Other prominent features were axial hypotonia, orolingual dyskinesia, pyramidal tract symptoms, eye movement abnormalities, choreiform movements, dystonia, including status dystonicus with oculogyric crises, and gastrointestinal complications. Parkinsonian symptoms, such as bradykinesia, rigidity, hypomimia, and tremor, tended to occur later. All patients had cognitive impairment and lack of speech, but reception and understanding were good. There was no effective and sustained treatment for the symptoms.

Four patients died between 9 and 16 years of age. Puffenberger et al. The proband developed irritability and feeding difficulties soon after birth, followed by generalized rigidity and dystonia during early infancy.

She had impaired motor development and severe rigid parkinsonism by late childhood. She could not speak or use her hands to communicate, and it was difficult to assess cognitive function or thought content. Brain structure was normal. Cerebrospinal fluid showed increased HVA. A similarly affected sister had died.

By linkage analysis followed by candidate gene sequencing of a consanguineous Pakistani family with infantile parkinsonism-dystonia, Kurian et al. A similarly affected individual from a second family had a different homozygous mutation PL; In vitro functional expression studies showed that both mutant proteins had no dopamine uptake activity. In 8 unrelated patients with dopamine transporter deficiency syndrome, Kurian et al. None of the patients shared a mutation, suggesting the absence of mutational hotspots.

In vitro functional expression studies in HEK cells showed that the mutations caused a loss of transporter function and decreased expression of the normal protein.

By homozygosity mapping followed by exome sequencing of a Mennonite family in which 2 sisters had infantile parkinsonism-dystonia, Puffenberger et al.

No carriers of this mutation were found among Mennonite control samples. This disorder is due to loss of function of the presynaptic dopamine transporter.

Defective reuptake of dopamine is thought to lead to accumulation of dopamine in the synapse, which is catabolized and causes increased CSF levels of HVA.

Poor dopamine reuptake leads to depletion of presynaptic stores of dopamine for extraneuronal release. Excess extraneuronal dopamine may also result in decreased production of dopamine and to downregulation or desensitization of dopamine receptors, thus mimicking dopamine deficiency review by Kurian et al. Kurian, M. The monoamine neurotransmitter disorders: an expanding range of neurological syndromes. Lancet Neurol. Clinical and molecular characterisation of hereditary dopamine transporter deficiency syndrome: an observational cohort and experimental study.

Homozygous loss-of-function mutations in the gene encoding the dopamine transporter are associated with infantile parkinsonism-dystonia. Puffenberger, E. Genetic mapping and exome sequencing identify variants associated with five novel diseases. PLoS One 7: e, Note: Electronic Article. A number sign is used with this entry because infantile parkinsonism-dystonia-1 PKDYS1 is caused by homozygous or compound heterozygous mutation in the SLC6A3 gene , which encodes a dopamine transporter DAT1 , on chromosome 5p NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers, and by advanced students in science and medicine.

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Gene Reviews. Genetic Alliance. Genetics Home Reference. MGI Mouse Phenotype. Clinical Synopsis Toggle Dropdown. Phenotypic Series Toggle Dropdown. PheneGene Graphics Linear Radial. Central Nervous System. Parkinsonism-dystonia, infantile - PS - 2 Entries.

Cassandra L. Creation Date:. Edit History:. Clinical Features. Molecular Genetics. Printed: June 4, Parkinsonism-dystonia, infantile, 1.

Parkinsonism-dystonia, infantile, 2. Autosomal recessive.








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